Abstract The goal of this High-End Instrumentation proposal is to enhance the molecular imaging capabilities of the University of Wisconsin Waisman Brain Imaging Laboratory (WBIL) and update our positron emission tomography (PET) imaging system. We are requesting funds to purchase the Siemens Biograph Horizon PET/CT scanner to replace our existing 17 year old scanner that is no longer vendor-supported. This commercially available system was selected based upon its state-of-the-art PET component and a more economical CT component (used exclusively for attenuation correction for our neuroimaging research). This system has an extended axial field of view (22cm) which provides an overall increased detection sensitivity, along with a more uniform sensitivity over the volume of the brain. This will result in dramatically improved SNR compared to our existing system. There are currently 9 major NIH-funded projects by University of Wisconsin investigators utilizing PET imaging as a primary outcome measure. These are heavily focused on measuring changes in amyloid and tau burden as presymptomatic biomarkers for Alzheimer?s disease using longitudinal study designs. Detecting these subtle changes (<10%) in amyloid and tau binding over the course of several years requires a stable, reliable and quantitatively accurate PET system over a long term. The Horizon PET/CT system will be 100% dedicated to research applications to overcome the challenge of integrating these multi-scan protocols into the schedule of a clinical scanner. UW researchers have directed a tremendous amount of resources into creating invaluable subject populations and we are now well-positioned to fully exploit the powerful PET molecular imaging measures in our investigations of neurodevelopment and neuropathology. This new PET/CT will ensure our future for uninterrupted acquisition of high quality data for this important research.